The age structure and stable isotope composition of a stalagmite (CC1) from an upland cave in central-western Italy were studied to investigate regional response to global climatic changes. Four growth phases are constrained by 28 thermal ionization and multi-collector inductively coupled plasma mass spectrometry Th–U ages and reveal intermittent deposition through the period between Marine Isotope Stage (MIS) 11 and 3 (∼380 and ∼43 kyr). Most of the growth took place between ∼380 and ∼280 kyr, a period punctuated briefly by a hiatus in deposition through the glacial maximum of MIS 10. Growth was terminated abruptly at 280 kyr just prior to the MIS 8 glacial maximum. With a present-day chamber temperature of 7.5 °C, the timing of hiatuses close to these glacial maxima point to freezing conditions at the time. No deposition was recorded through the entirety of MIS 7 and most of MIS 6, whilst two minor growth phases occurred at ∼141–125 and ∼43 kyr. Growth at 141 kyr indicates temperatures >0 °C at a time when MIS 6 ice volumes were close to their maximum. High stable carbon isotope (δ¹³C) values (−2.8‰ to +3.1‰) throughout the stalagmite's growth reflect a persistently low input of biogenic CO², indicating that the steep, barren and alpine-like recharge area of today has been in existence for at least the last ∼380 kyr. During MIS 9, the lowest δ¹³C values occur well after maximum interglacial conditions, suggesting a lag in the development of post-glacial soils in this high-altitude karst. The stable oxygen isotope (δ¹⁸O) trends match the main structural features of the major climate proxy records (SPECMAP, Vostok and Devils Hole), suggesting that the δ¹⁸O of CC1 has responded to global-scale climate changes, whilst remarkable similarity exists between CC1 δ¹⁸O and regional sea-surface temperature reconstructions from North Atlantic core ODP980 and southwest Pacific marine core MD97-2120 through the most detailed part of the CC1 record, MIS 9–8. The results suggest that CC1 and other stalagmites from the cave have the potential to capture a long record of regional temperature trends, particularly in regards to the relative severity of Pleistocene glacial stages.